Overview

• Definition: Pompe disease is a lysosomal storage disorder caused by defective glycogenolysis, leading to glycogen accumulation in lysosomes.
• Pathophysiology:
  • Lysosome rupture leads to tissue damage.
  • Primarily affects skeletal and cardiac muscles.

Clinical Presentation

• Infantile-Onset Pompe Disease (IOPD):
  • Onset: First few months of life.
  • Symptoms:
    • Muscle weakness and hypotonia.
    • Developmental delay.
    • Feeding difficulties and failure to thrive.
    • Macroglossia (enlarged tongue).
    • Hypertrophic cardiomyopathy.
  • Outcomes without treatment:
    • Death from heart failure in the first year of life.
  • Survivors may require:
    • Respiratory support (e.g., mechanical ventilation).
    • Feeding tubes, walkers, and/or wheelchairs.
• Late-Onset Pompe Disease (LOPD):
  • Onset: Childhood to adulthood.
  • Symptoms:
    • Proximal muscle weakness.
    • Normal heart function in adult-onset cases.
  • Disease progression:
    • Earlier onset correlates with more severe and faster progression.

Diagnosis

• Clinical Presentation:
  • Symptoms of muscle and/or cardiac involvement.
• Tests:
  • Measurement of alpha-glucosidase enzyme activity in blood.
  • Molecular testing showing pathogenic variants in the GAA gene.
  • Supportive findings:
    • Elevated creatine kinase (CK).
    • Elevated urine hexose tetrasaccharide (Hex4).

Treatment

• Enzyme Replacement Therapy (ERT):
  • Drugs: Alglucosidase alfa (Myozyme®, Lumizyme®).
  • Impact on IOPD:
    • Treats hypertrophic cardiomyopathy.
    • Improves left ventricular mass index and other cardiac parameters.
    • Limited skeletal muscle response, leaving residual neuromuscular impairments.
  • Impact on LOPD:
    • Stabilizes respiratory capacity.
    • Improves motor function and maintains ambulation.
    • Increases survival.
• Ongoing Challenges:
  • Weakness, hypotonia, dysarthria, and dysphagia persist in many IOPD patients.
  • High dependency on assistive devices and respiratory support.

Multidisciplinary Care

• Required due to chronic nature and multisystem involvement.
• Includes:
  • Neurologists, cardiologists, pulmonologists, dietitians, and physical therapists.
• Clinical guidelines available for both IOPD and LOPD.

Prognosis

• Pre-ERT Era:
  • Fatal cardiac disease in infants.
• Post-ERT Era:
  • Chronic neuromuscular disorder.
  • Improved survival and quality of life with multidisciplinary management.

Key Points

• Early diagnosis and initiation of ERT are critical.
• Comprehensive and long-term care is essential for managing complications.